Single-cell sequencing reveals the landscape of the tumor microenvironment in malignant fibrous histiocytoma

Abstract Malignant fibrous histiocytoma (MFH) is an invasive pleomorphic soft tissue sarcoma with a high degree of malignancy and poor prognoses, and is prone to recurrence and metastasis. The pathophysiology remains elusive and its therapeutic options are limited. The 5-year recurrence rate of patients is 36–61%. Progress in single-cell RNA sequencing (scRNA-seq) provides an opportunity to dissect the pathophysiology of human diseases at unprecedented resolution, particularly in the diseases lacking animal models, such as MFH. We performed scRNA-seq on tumor tissues and adjacent muscle tissues from a patient with MFH. We identified Cell types and the corresponding marker genes by single-cell RNA sequencing. Malignant cells of fibroblasts were evaluated by CopyKAT analysis and differentially expressed genes of sequencing. We identified PDCD1, CTLA4 and TIGIT as potential targets. We further showed that C2_Exhausted CD4 + Treg and C1_Exhausted CD8 + T cell highly expressed PDCD1, CTLA4 and TIGIT. Intervention via PD-1 immune checkpoint inhibitor (tirelizumab) enabled disease control and reduced tumor immunosuppression. Thus, scRNA-seq analyses guide a successful therapeutic intervention in the MFH patient, improve our understanding of complex human diseases and provide an alternative approach to personalized medicine.